Anxiety disorders are illnesses of which the main symptoms are manifestations of unrealistic or excessively pronounced anxiety. In the case of phobias, to the sub-types of which so-called simple phobias, social anxiety disorders and agoraphobias belong, the anxiety attacks are associated with particular objects or situations. However, pronounced anxiety attacks can also occur without being triggered by specific situations or circumstances. Thus panic disorders are distinguished by recurring, pronounced anxiety attacks which are not foreseeable and therefore lead to anticipatory anxiety. Generalized anxiety disorders are floating, lasting anxieties with diverse, in particular vegetative symptoms. Patients who suffer from posttraumatic stress disorders (PTSD) were exposed to a brief or long-lasting event or occurrence of exceptional threat or with catastrophic proportions. This event would induce a deep-seated despair in virtually anyone. Those affected live through the stresses again and again in quick-fire images, accompanied by psychovegetative symptoms, such as, inter alia, severe outbreaks of perspiration and a racing heart. Obsessive compulsive disorders (OCD) are characterized by recurring unpleasant thoughts, impulses or actions which last several weeks, are experienced as being part of the self and against which at least partial resistance is given since the person affected finds them senseless. Mixed anxiety disorders or anxiety disorders accompanied with depressions very often exist.
Depressions are affectivity disorders in which a depressive syndrome is of prime significance, depressive meaning associated with depression or of sad mood. The depressive illnesses include unipolar severe depressions with or without delusion, moderate depressions, mild depressions, dysthymia, melancholy, bipolar depressions (bipolar illness I, mania and severe depression; bipolar illness II, hypomania and severe depressions; cyclothymic personality disorders, hypomania and mild depressions).
Those pharmaceutical formulations with an anxiolytic and antidepressant action based on an inhibition of the reuptake of the monoamines noradrenaline and/or serotonin are widely used for therapy of anxiety disorders and depressions (Pacher, P., Kohegyi, E., Kecskemeti, V., Furst, S., Current Medicinal Chemistry 2001, 8, 89-100; Goddard, A. W., Coplan, J. D. Gorman, J. M., Charney, D. S., in: Neurobiology of mental illness, Charney, D. S., Nestler, E. J., Bunney, B. S. (eds.), Oxford University Press, New York, 1999, p. 548-563). A great disadvantage in this context is that the monoamine reuptake inhibitors display their anxiolytic and antidepressant action only after several weeks of treatment and achieve their full activity only after approx. 3-4 weeks. At the start of treatment of patients suffering from anxiety, and also those suffering from depression, standard medications frequently intensify or induce anxiety states, unrest, increased irritability and thoughts of suicide. These psychomotor states of excitation and thoughts of suicide occur particularly frequently in the first days after the start of therapy both with tricyclic antidepressants, selective serotonin reuptake inhibitors (so-called SSRIs) and with mixed serotonin-noradrenalin reuptake inhibitors, and are associated with an increased risk of suicide (Jick, H., Kaye, J. A., Jick, S. S.: Antidepressants and the risk of suicidal behaviours, JAMA (2004) 292, 338-343). This results in the need for strict monitoring of patients being treated with standard antidepressants, and possibly for a reduction in the dose. For anxiety disorders and depressions there is therefore a great need for a therapy which is distinguished by an early onset of action and causes no anxiogenic side effects and therefore no increased risk of suicide at the start of therapy, or inhibits those induced by antidepressants.
Since approx. 20-30% of patients suffering from anxiety disorders and depressions show no improvement after treatment with approved antidepressants and anxiolytics, new therapeutic systems for treatment of hitherto pharmacotherapy-resistant patients are of high benefit.
The monoamine reuptake inhibitors used for therapy of anxiety disorders and depressions are also used for treatment of chronic pain patients. In addition to the actual antidepressant and anxiolytic actions, reuptake inhibitors of noradrenaline and serotonin lead to an independent analgesic action in that descending pain inhibition pathways at the level of the spinal marrow are activated. Monoamine reuptake inhibitors are employed clinically for monotherapy of neuropathic pain, and also as an adjuvant to opiates for treatment of chronic pain (inter alia inflammatory pain, tumour pain, fibromyalgia) (Sindrup, in: Yaksh, T. L., et al., Anesthesia. Biological foundations. Philadelphia: Lippincott-Raven, 1997, 987-997). Since chronic pain is accompanied by anxiety disorders or depressions in a large number of patients, a substance with μ-opiate agonistic properties combined with a clinically relevant serotonin and/or noradrenaline reuptake inhibition is particularly favourable.